{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T17:18:47Z","timestamp":1786295927017,"version":"build-2736575974"},"reference-count":29,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genes Chromosomes &amp;amp; Cancer"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Epstein\u2013Barr virus\u2010associated gastric cancer (EBVaGC) is a distinct histological and molecular subtype of gastric cancer. Histologically, it is characterized by marked lymphocytic infiltration; molecularly, it exhibits a hypermethylated phenotype. The diagnosis of surgical pathology relies on the detection of BEV\u2010encoded RNA in\u00a0situ hybridization (EBER\u2010ISH) in tumor cells. To diagnose the histological type related to EBV is crucial, as EBVaGC is a potential target for treatment with programed cell death\u20101\/programed cell death ligand\u20101 inhibitors. This study comprehensively analyzed viral and tumor gene expression in EBVaGC using RNA sequencing (RNA\u2010seq). Six cases of EBVaGC, including one with heterogeneous EBER\u2010ISH expression, were investigated. RNA was extracted from formalin\u2010fixed, paraffin\u2010embedded tissue sections and analyzed using RNA\u2010seq. EBER\u2010ISH\u2010positive and negative areas from tumors with heterogeneous EBER\u2010ISH expression were separately collected using modified manual microdissection techniques. EBV gene expression in EBVaGCs varied among the tumors. Viral gene expression was observed even in EBER\u2010ISH\u2010negative lesions in tumors showing heterogeneous EBER\u2010ISH expression. Gene expression and set enrichment analyses revealed that EBVaGC was highly immunogenic, whereas EBER\u2010ISH\u2010negative lesions were not. However, EBVaGC tumor gene expression patterns, including EBER\u2010ISH\u2010negative lesions, were classified into the same cluster. Viral RNA expression in EBVaGC was heterogenous and even\n                    <jats:italic>EBER<\/jats:italic>\n                    expression fluctuates, suggesting that EBV infection in EBVaGC may not be detected by EBER\u2010ISH alone.\n                  <\/jats:p>","DOI":"10.1002\/gcc.70117","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T10:10:08Z","timestamp":1773483008000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive\n                    <scp>RNA<\/scp>\n                    Sequencing Analysis Reveals Heterogeneous Expression of Epstein\u2013Barr Virus Genes in Gastric Cancer"],"prefix":"10.1002","volume":"65","author":[{"given":"Yasuko","family":"Fujita","sequence":"first","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Aichi Cancer Center  Nagoya Japan"},{"name":"Division of Translational Oncoimmunology Aichi Cancer Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuhiro","family":"Masago","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Aichi Cancer Center  Nagoya Japan"},{"name":"Division of Translational Oncoimmunology Aichi Cancer Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiichi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Pathology and Molecular Diagnostics Aichi Cancer Center  Nagoya Japan"},{"name":"Division of Translational Oncoimmunology Aichi Cancer Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Kobe Central Hospital  Kobe Hyogo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Seto","sequence":"additional","affiliation":[{"name":"Division of Translational Oncoimmunology Aichi Cancer Center  Nagoya Japan"},{"name":"Department of Thoracic Surgery Aichi Cancer Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kuroda","sequence":"additional","affiliation":[{"name":"Division of Translational Oncoimmunology Aichi Cancer Center  Nagoya Japan"},{"name":"Department of Thoracic Surgery Teikyo University Mizonokuchi Hospital  Kawasaki Kanagawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitsugu","family":"Horio","sequence":"additional","affiliation":[{"name":"Division of Translational Oncoimmunology Aichi Cancer Center  Nagoya Japan"},{"name":"Department of Thoracic Oncology Aichi Cancer Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Division of Translational Oncoimmunology Aichi Cancer Center  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/apm.1965.64.1.31"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13480"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120\u2010021\u201001215\u20103"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/v15030714"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16050991"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.271734"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1996.412"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i5.629"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prp.2022.154108"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx047"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa859"},{"key":"e_1_2_11_14_1","first-page":"1063","article-title":"Association 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